The diagnosis and treatment of prostate cancer will benefit greatly from the availability of simple, inexpensive blood tests which enable clinicians to distinguish more accurately between aggressive and non aggressive tumors. The long-term goal of this SBIR project is to develop a clinical assay which measures serum levels of several prostate tumor-associated antibodies. This information, when combined with more traditional diagnostic tests, will assist physicians in judging the metastatic potential of a developing tumor and will thus exclude many unnecessary biopsies. The proposed Phase I studies are designed to establish proof of concept of a novel Phage Microarray technology for discovering previously unknown tumor-related antibodies in the sera of patients in the early and later stages of the disease. DSI's new approach uses a novel application of phage display technology to identify not only tumor-specific autoantibodies, but also tumor associated antibodies which are naturally present at low levels in normal sera but are significantly elevated as a tumor progresses. This strategy avoids the costly and time-consuming purification of tumor antigens and makes it possible to detect autoantibodies reactive with post-translational modifications, such as tumor associated changes in glycosylation. The Phase I goals are focused on achieving two Specific Aims:1. Select and individually amplify 10,000 phage peptide clones which bind to antibodies in pooled sera from prostate cancer patients; and 2. Incorporate the phage clones into a microarray format and screen individual serum samples from patients with low and high levels of PSA and from healthy controls. During Phase II of this project, the immunoreactive peptides will be used to develop an economical clinical assay for profiling serum levels of prostate tumor-associated autoantibodies. This assay has the potential to become a standard diagnostic procedure for the early detection of prostate cancer and would have a significant world-wide market.